Platform rockers are very commonly used in biology laboratories. Typically, a platform tilts back and forth, in a fashion similar to a see-saw or teeter-totter. The user may place containers of liquids and/or other items, on the platform. This see-saw action keeps the contents of the containers mixed. The rocking see saw action is used for many applications, such as culturing cells, staining gels, and hybridization of nucleic acids. In most platform rockers, the motor runs at a selectable, constant speed, typically in the realm of 10 to 60 rocking cycles per minute. A motor turns a cam or 4-bar linkage, connected to the platform. As the cam rotates at a constant speed, it drives a linkage causing the platform to tilt back and forth. While this is good for some applications, there are many other applications that require an advanced platform rocker able to adjust the rocking parameters as a function of time or in response to signals from sensors or other devices. In addition, an advanced platform rocker that can vary the range of tilt can use the action of tilting the platform to perform other functions.
One very common application of platform rockers entails the staining of blots and gels. Blots and gels are widely used in molecular biology to separate and distinguish nucleic acids and proteins. In Western Blots, also called protein immunoblots, there is a series of reagents and wash buffers that interact with the blots. Similar, although shorter, protocols are used with other immunoassays for nucleic acids. Typically the first step entails electrophoresis to cause the nucleic acids or proteins to travel through a gel at different rates depending upon size and charge. Bands in a gel can be transferred to a blot. The bands can be imaged using reagents that bind to the bands and then washing steps remove the reagents which are not attached to the bands. The images reveal the size and charge of the nucleic acids or proteins. The nucleic acids or proteins of interest can be selectively removed for further analysis. The binding and washing steps typically require manual labor to add and remove the reagents and wash buffers. While several automated instruments exist, they have shortcomings. For example they require complex plumbing with multiple pumps and/or valves, and relatively large volumes of reagents. This patent covers innovative features for an advanced rocker capable of manipulating volumes of liquids, thereby foregoing these limitations.
Typically, the steps involving incubation with reagents and washing is performed in a flat bottomed tray. To reduce the volume of reagent required to react with the blot, the blot can be placed in a bottle on a bottle roller, whereby a minimal volume of liquid washes over the blot or gel as the bottle rotates. Gravity and the shape of the bottle ensure that the liquid covers the entire blot laterally. In a flat bottomed tray, to ensure complete coverage laterally across the blot or gel, a much larger volume of liquid is required. An advanced rocker, cable of holding trays with convex bottoms, simulating the cylindrical shape of a bottle, and pivoting near the axis of curvature of the bottom surface of the trays, enables the use of smaller volumes of reagents. Ideally, the incubation with antibodies is performed at a slow rocking speed, while the washing steps are more vigorous. With an advanced platform rocker, the dispensing of liquids into the trays and removal of the liquids from the trays can be accomplished without valves, pumps or tubing.
This invention can also be used for other procedures that entail reactions with reagents and/or washing of samples, such as fluorescence in situ hybridization (FISH), a technique that requires many steps involving reagents and washing.
There are other applications in which a platform rocker that performs a series of cycles, in which each cycle comprises a series of steps, would enable better results. For simplicity, we will call these advanced rocking routines. For example, in hybridization of nucleic acids, depletion zones form in the liquid as free molecules bind to those attached to the substrate. A symmetric routine is not efficient at mixing the liquid in this low Reynolds number situation. An asymmetric routine, however, in which the platform pauses at a steeper angle in one direction, and then at a less steep angle in the other, enables better microfluidic mixing, and thus, better hybridization results. The advanced platform rocker described here can also rock at extremely low rocking speeds for specialized applications, such as just several rock cycles per hour, or rock once or twice, then wait a day before repeating this cycle. This is advantageous for containers that are in storage with contents that would otherwise settle. Such an advanced platform rocker is also beneficial for viral transduction. In this process, scientists desire a periodic routine that allows diffusion to occur while their sample is stationary, allowing the molecules to interact with the substrate, for perhaps fifteen minutes, and then recharges the depletion region by rocking their sample, thereby mixing their solution. Currently, the rocking is started and stopped manually. In some washing and mixing applications, a high frequency but low amplitude agitation superimposed upon a low frequency, high amplitude agitation would provide better washing or mixing. Likewise, some microfluidic applications require gravity to force a small amount or portion of liquid from one section of the microfluidic device to another according to a particular schedule.